Rheumatoid Arthritis (RA) is a debilitating disease which affects nearly 1% of the US population. It initially attacks the small joints of the hand and foot. Recent RA research shows that early aggressive therapy is most effective, making early diagnosis essential. Currently the early subtle tissue effects of RA are best imaged with MRI and ultrasound. While having good contrast for joint soft tissues, these methods lack enough spatial resolution for small joints such as those of the hand. In recent years a new X-ray imaging method based on X- ray differential phase contrast (DPC) has been developed with high spatial resolution and excellent imaging of soft tissues that are nearly invisible on conventional x-rays. Recent experiments using synchrotron X-rays demonstrate that DPC can image with high resolution soft tissues such as cartilage and ligaments in the joints of the hand, knee and ankle. DPC has the potential to improve contrast and resolution at comparable or lower doses than used in conventional, absorption based X-ray imaging. The long term goal of our project is to develop a commercial DPC enhanced X-ray imaging system, which will enable clinical imaging of soft tissues in the small hand joints with better than 100 5m resolution and at low doses. Such systems will help rheumatologists to more accurately identify patients that are appropriate for aggressive therapeutic regimens and to more sensitively monitor patients over the course of their disease. The system will be based on the Talbot interferometer method, which can work with medical X-ray tubes and which uses ultra-fine gratings to angularly filter the transmitted X-rays. A preliminary study shows that such a system could be built using an interferometer of 25-35 keV mean energy, together with a W anode mammography type X-ray tube and a small pixel CCD detector. The incident spectrum is matched to the spectral response of the interferometer using K-edge filters (Z =47-56). This also reduces the skin dose to a few tens of 5Gy, at typical exposures time of a fraction of a second. The few-5m-period gratings needed for such a system can be produced by nanofabrication methods and have become recently commercially available. In Phase-I of the project we will investigate the feasibility and merit of the interferometer method for DPC imaging of the small hand joints. The first aim will be to build and calibrate a 'bench-top'test DPC system, which will enable flexible adjustment of the interferometer parameters. The second aim will be to use this system to demonstrate and optimize the DPC imaging of joint soft tissue on animal and cadaver samples. In Phase-II we plan developing a prototype system for clinical research of RA diagnosis using DPC enhanced X-ray imaging and tomosynthesis. The system will be implemented and tested at the JHU Division of Rheumatology in collaboration with JHU physicians. In addition, there are efforts at the JHU Department of Physics and elsewhere to develop phase-contrast optics for higher X-ray energy. This will allow development at later stages of DPC systems suitable for imaging of large joints such as the knee. PUBLIC HEALTH RELEVANCE: Rheumatoid Arthritis (RA) affects more than 1% of the worldwide population. Characterized by joint swelling, stiffness, and pain, the condition leads to progressive joint destruction and disability and can involve most of the joints in the body. The small joints of the hands, wrists, and feet are commonly affected early in disease progression. This proposed phased-contrast X-ray system for the hands should provide imaging of soft tissue damage that is nearly invisible on conventional x-rays. The system should provide better identification of patients with RA and more sensitive monitoring of disease progression and the effects of treatment.